ToxT: Difference between revisions

The crystal structure of ToxT is resolved in monomeric form, after isolation from <i>Vibrio cholerae</i> strain O395.<ref name="structure">PMID: 20133655</ref>

==Introduction==

<b>ToxT</b> is a molecule at the end of a transcriptional cascade that autoregulates the transcription of the primary virulence factors of <i>Vibrio cholerae</i>[http://en.wikipedia.org/wiki/Vibrio_cholerae] and itself. ToxT is a cytoplasmic protein that is activated in turn by ToxR, which is itself activated by ToxS in response to environmental stimuli.<ref>Kenneth Todar [http://www.textbookofbacteriology.net/cholera.html] ''Vibrio cholerae'' and Asiatic Cholera, Todar's Online Textbook of Bacteriology. Date of access: 2011-11-28.</ref>  These two factors, cholera toxin (CT)[http://en.wikipedia.org/wiki/Cholera_toxin] and the toxin co-regulated pilus (TCP), are instrumental in causing the disease <b>cholera</b>[http://en.wikipedia.org/wiki/Cholera]. This is an intestinal infection resulting in massive water loss in the affected individual, causing extreme dehydration.[http://en.wikipedia.org/wiki/Cholera] Rehydration is sufficient as treatment.

==Structural Features==

<u>DNA-binding</u>. ToxT belongs to a family of transcriptional regulators headed by and known as AraC.<ref name="structure">PMID: 20133655</ref> The AraC family is characterized by a 100 amino acid region of sequence similarity that forms a <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Two_hth_domains/1'>DNA-binding domain</scene> with two helix-turn-helix motifs (one on either side of the black linker). <ref name="arac">PMID: 11282467</ref> This DNA binding domain is composed of seven alpha helices. HTH1 is composed of alpha helices five and six, while HTH2 is composed of alpha helices eight and nine. The two HTH regions are linked by the very polar alpha helix seven(shown in black). The overall domain is located at the C-terminus.<ref name="structure">PMID: 20133655</ref> Assuming ToxT is similar in mechanism to other AraC proteins, helix six from HTH1 and helix nine from HTH2 become aligned with the help of helix seven. Helix seven is positioned to attach to the N terminal binding pocket(the polar linking region) to allow binding to major consecutive grooves of target DNA (specific promoters for virulence genes).<ref name="structure">PMID: 20133655</ref>[http://www.pnas.org/content/107/7/2860/F3.large.jpg]. The conformation of helix seven is dependent on the ligand bound.